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Acoustic Stimulation Promotes DNA Fragmentation in the Guinea Pig Cochlea

Tomonobu Kamio^1,2, Ken-ichi Watanabe¹ and Kimihiro Okubo¹

¹Department of Otorhinolaryngology, Graduate School of Medicine, Nippon Medical School
²Kamio Memorial Hospital

Apoptosis can be described as programmed cell death. Apoptosis regulates cell turnover and is involved in various pathological conditions. The characteristic features of apoptosis are shrinkage of the cell body, chromatin condensation, and nucleic acid fragmentation. During apoptosis, double-stranded DNA is broken down into single-stranded DNA (ssDNA) by proteases. Acoustic trauma is commonly encountered in otorhinolaryngology clinics. Intense noise can cause inner ear damage, such as hearing disturbance, tinnitus, ear fullness, and decreased speech discrimination. In this study, we used immunohistochemical and electrophysiological methods to examine the fragmentation of DNA in the cochleas of guinea pigs that had been exposed to intense noise. Twenty-four guinea pigs weighing 250 to 350 g were used. The animals were divided into 4 groups: (I) a control group (n=6), (II) a group that was exposed to noise for 2 hours (n=6), (III) a group that was exposed to noise for 5 hours (n=6), and (IV) a group that was exposed to noise for 20 hours. The stimulus was a pure tone delivered at a frequency of 2 kHz. The sound pressure level was 120 dBSPL. No threshold shifts were apparent in group I. Group II showed a significant elevation of the hearing threshold (ANOVA, p<0.05^*). The ABR threshold level was also significantly elevated immediately after the acoustic stimulation in groups III and IV (ANOVA, p<0.01^**). In groups I, II, and IV, the lateral wall of the ear did not show immunoreactivity to ssDNA but did in group III. No immunoreactivity was apparent in the organ of Corti in group I or II. However, the supporting cells and outer hair cells in groups III and IV showed reactions for ssDNA. The fine structure of the organ of Corti had been destroyed in group IV. The lateral wall showed immunoreactivity for ssDNA only in group III, whereas the organ of Corti showed reactions for ssDNA in groups III and IV. Our study suggests that apoptotic changes occur in patients that suffer acoustic trauma. Once the apoptotic pathway has started, it is irreversible. Thus, early diagnosis and treatment are necessary. Earplugs should also be worn at rock concerts.

J Nippon Med Sch 2012; 79: 349-356

Keywords
apoptosis, single-stranded DNA, acoustic trauma, free radicals

Correspondence to
Ken-ichi Watanabe, MD, PhD, Department of Otorhinolaryngology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
bxp02646@nifty.com

Received, February 6, 2012
Accepted, March 21, 2012